tbuckley/cabot-search huggingface dataset:
Immune therapy related adverse events in metastatic non-small cell lung carcinoma patients at a rural academic center.
Authors: Melisa Pasli, Mahvish Muzaffar, Radhamani Kannaiyan
Journal: Journal of Clinical Oncology (2023)

e21203 Background: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for stage IV non-small cell lung cancer (NSCLC) patients. Immune related adverse events (irAEs) are the diverse immunologic side effects of patients receiving ICIs and may result in significant patient morbidity, subsequently impacting quality of life. If severe enough, irAEs may lead to hospitalization and may necessitate administration of immunosuppressants or IL-6 receptor antagonists. Our study sought to characterize irAEs in a patient population receiving ICIs at a rural tertiary care center. Methods: This was an IRB-approved retrospective cohort study using SPSS version 28. Patients with stage IV NSCLC receiving ICIs at ECU Health Medical Center were analyzed and 190 patients met inclusion criteria. Results: Of our cohort, 66.3% (n = 126) experienced at least one irAE of any grade, 46.3% (n = 88) were hospitalized due to grade 3 or 4 irAE, 55.7%(n = 106) were either started on steroids or had a dose increase to treat the irAE, 48.9% (n = 93) received immunosuppression to treat the irAE, and 41.5% (n = 79) had immunotherapy held either temporarily or permanently due to the irAE. 25.7% (n = 49) were rechallenged and 18.9% (n = 36) experienced an irAE after being rechallenged. 34.7% (n = 66) experienced pneumonitis, 22.1%(n = 42) constitutional symptoms, 17.8%(n = 34) gastrointestinal, 10.5%(n = 20) neurological, 10.5%(n = 20) dermatological, 6.8%(n = 13) endocrine, 3.6%(n = 7) hematological, 3.1%(n = 6) musculoskeletal, and 3.1%(n = 6) cardiovascular irAEs. When adjusting for race, sex, line of therapy, and histological type, logistic regression analysis yielded no significant difference in the probability of developing an irAE when comparing patients treated with nivolumab versus atezolizumab and pembrolizumab. Patients treated with atezolizumab (OR:0.17; p = 0.020; 95% CI:0.039-0.757) and pembrolizumab (OR:0.20; p = 0.021; 95% CI:0.055-0.785) were less likely to be hospitalized for an irAE when compared to patients treated with nivolumab. When rechallenged, no difference was noted in recurrent irAE development when comparing pembrolizumab and nivolumab. Cox regression analysis demonstrated that patients treated with atezolizumab (OR:0.36; p = 0.010; 95% CI:0.167-0.781) and pembrolizumab (OR:0.29; p &lt; 0.001; 95% CI:0.291-0.148) had better OS when compared to nivolumab. No difference was evident when comparing White and Black patients experiencing any grade irAE (n = 69, n = 53), grade 3 or 4 irAE (n = 44, n = 40), OS (n = 104, n = 80), and PFS (n = 104, n = 80). Conclusions: Our demonstrated irAE side effect profile is similar to those of published studies. No racial disparities were noted in our cohort when analyzing for any grade irAEs, grade 3 or 4 irAEs, OS, and PFS. Our study yields clinically pragmatic insight into better understanding how various factors, such as ICI selection and race, may impact patient outcomes.
The impact of COVID-19 on anxiety among breast cancer survivors before, during and after the pandemic.
Authors: Edison Tsui, Katherine Reeves, Isabella Caruso, Grace Makari-Judson
Journal: Journal of Clinical Oncology (2023)

e24178 Background: The COVID-19 pandemic has caused unprecedented stressors on the mental health of patients with cancer as well as with cancer survivors. Little is known regarding anxiety among breast cancer survivors during and following the pandemic. Methods: We performed a cross-sectional study evaluating the mental health impacts of the COVID-19 pandemic on a cohort of breast cancer survivors (n = 1333). Between January and March 2022, participants enrolled in the Rays of Hope Breast Cancer Research Registry were invited to complete an online study questionnaire. We analyzed the data collected from a series of questions regarding outcomes and perspectives representing three distinct time periods: before (prior to March 2020), during (March 2020-June 2021) and after the COVID-19 pandemic (January-March 2022), based on the dates of the Massachusetts State of Emergency declaration. The COVID-19 Anxiety Scale (CAS) was used to measure anxiety specific to COVID-19. Generalized anxiety symptoms were measured using the Generalized Anxiety Disorder 7-item (GAD-7) scale. Multinomial logistic regression was used to identify factors related to increased or decreased anxiety symptoms. Results: A total of 272 independent participants (21.5%) completed the survey. Of these, 230 respondents with a confirmed history of breast cancer were included in the final analysis. While 26.2% met GAD-7 criteria for moderate to severe anxiety after the pandemic, only 13% self-reported a prior diagnosis of any mental health condition. Approximately 17% reported experiencing more anxiety symptoms after the pandemic compared to before. A history of smoking was associated with a higher likelihood of experiencing increased symptoms of generalized anxiety (OR = 1.97, 95% CI 0.93-4.14); whereas exercise frequency of at least three times per week was associated with experiencing a decrease in anxiety symptoms over this period (OR = 7.00, 95% CI 1.39-35.14). The CAS and reporting that the pandemic had a negative impact on cancer care were associated with a higher likelihood of increased generalized anxiety after the pandemic (OR = 2.21, 95% CI 1.19-4.09; OR = 3.05, 95% CI 1.06-8.83, respectively). Conclusions: Increased symptoms of anxiety were prevalent among breast cancer survivors during the pandemic and, in some, have not returned to pre-pandemic levels. Less than half of participants with symptoms meeting criteria for moderate to severe anxiety reported having a formal medical diagnosis, suggesting that clinically significant anxiety may be underrecognized in breast cancer survivors following the pandemic.
Benefit of post-operative radiation therapy for incompletely resected stage I-IIIA non-small cell lung cancer: An analysis of the National Cancer Database.
Authors: Sindu Iska, Mohamed Mohanna, Saad Sabbagh, Barbara Dominguez, Mira Itani, Hong Liang, Rafael Arteta-Bulos, Zeina A. Nahleh, Evan W. Alley
Journal: Journal of Clinical Oncology (2023)

8558 Background: The presence of micro-residual (R1) or macro-residual (R2) disease in non-small cell lung cancer (NSCLC) is associated with a higher risk of recurrence. The benefits of post-operative radiation therapy (PORT) in incompletely resected NSCLC is not clear. The purpose of this study is to compare median overall survival (mOS) of treatment modalities in the post-operative setting for resected stage I-IIIA NSCLC with residual disease (R1/R2) and to determine if PORT provides benefit in this patient population using the National Cancer Database (NCDB). Methods: From the NCDB dataset for the years of 2006-2016, we extracted patients diagnosed with stage I-IIIA NSCLC and who had incomplete resection with residual disease (R1/R2). Kaplan-Meier analysis was performed to differentiate the effect of different post-operative treatment modalities, concurrent chemo-radiotherapy (CCRT), sequential chemo-radiotherapy (SCRT) and chemotherapy (CT) alone on mOS. Subsequently, univariate Cox regression was used to identify statistically significant variables, then multivariate Cox regression was performed to establish variables that contributed to the survival. Lastly, multinomial logistic regression was utilized to establish association of the independent factors. SAS version 9.4 was used to analyze the data. Results: Among the 2701 patients who met inclusion criteria, the average age was 64.1, 64.8 and 65.9 year old for CCRT, SCRT and CT, respectively. Male's constituted 53.6% and white's were 88.1%, and patient's were distributed equally across clinical stages. The majority of patients received SCRT (51.7%) followed by CT alone (39%), and CCRT (9.2%). There were no statistically significant differences in mOS between the different treatment modalities (p=0.220). Patients with R2 were 177% more likely to receive CCRT than CT compared to R1 (OR 2.77, CI 1.86-4.13 and p&lt;0.001). Male's were 28% more likely to receive SCRT than CT compared to females (OR 1.28, CI 1.08-1.52 and p=0.0041). Nodal involvement was associated with decreased mOS with N2/N3 having 37% lower mOS compared to N0 (HR=1.37, CI 1.19-1.57 and p&lt;0.0001). Patients who had R2 disease had a 38% lower mOS compared to those R1 (HR 1.38%, CI 1.19-1.62, p&lt;0.0001). Conclusions: Despite the risk of unfavorable outcomes for patients with residual disease after surgery for NSCLC, the addition of radiotherapy, either concurrently or sequentially, to CT did not offer statistically significant mOS benefit compared to CT alone. Given the known toxicities of radiation, and the lack of impact on survival, the benefit of post-operative radiation is questionable among patients with residual disease after resection.
Circulating tumor DNA (ctDNA) status and clinical outcomes in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL) in the POLARIX study.
Authors: Alex Francisco Herrera, Samuel Tracy, Laurie Helen Sehn, Fabrice Jardin, Georg Lenz, Marek Trneny, Gilles A. Salles, Christopher Flowers, Herve Tilly, Jeff Porter Sharman, Jonathan W. Friedberg, Sandhya Balasubramanian, Vibha Raghavan, Jamie H. Hirata, Calvin Lee, Yanwen Jiang, Franck Morschhauser
Journal: Journal of Clinical Oncology (2023)

7523 Background: the POLARIX study, pts with previously untreated DLBCL were randomized to Pola-R-CHP or R-CHOP (NCT03274492; Tilly et al. 2022). We previously validated the prognostic value of ctDNA at baseline and after one cycle of therapy in POLARIX (Herrera et al. 2022); here, we evaluate the relationship between ctDNA clearance and PFS and OS. Methods: Pts were included if baseline and longitudinal ctDNA results were available. Plasma ctDNA was measured at baseline, Cycle (C) 5 Day (D) 1, and end of treatment (EOT), with the AVENIO NHL CAPP-Seq assay (Stokowski et al. 2022). ctDNA clearance was determined as previously described (Herrera et al. 2022). PFS and OS according to ctDNA status were reported as landmarked hazard ratios (HR) and 3-yr rates. HRs were adjusted for IPI score (&gt;2), region, bulky disease (&gt;7.5cm), age (&gt;60 years), and cell of origin. Results: At baseline, 654 pts had ctDNA results; 494 (76%) and 519 (79%) pts were evaluable at C5D1 and EOT, respectively. Undetectable ctDNA (ctDNA−) was achieved by 57% (152/265) of Pola-R-CHP-treated pts and 59% (135/229) of R-CHOP-treated pts at C5D1 (p=0.79), and by 66% (172/262) of Pola-R-CHP-treated pts and 67% (172/257) of R-CHOP-treated pts at EOT (p=0.83). Achieving ctDNA− was prognostic for PFS and OS in each treatment arm at C5D1 and EOT (Table). Pts in the Pola-R-CHP arm who had complete response (CR) with PET-CT and ctDNA− at EOT had superior PFS and OS compared with pts with CR and detectable ctDNA (ctDNA+) at EOT (PFS HR 0.30, 95% confidence interval [CI]: 0.14–0.66; OS HR 0.20, 95% CI: 0.07–0.60). This was not observed with R-CHOP (PFS HR 0.74, 95% CI: 0.34–1.63; OS HR 1.11, 95% CI: 0.30–4.16). Among pts with CR and ctDNA− at EOT, pts treated with Pola-R-CHP had superior PFS vs R-CHOP (HR 0.41, 95% CI: 0.21–0.82); this was not observed with OS (HR 0.41, 95% CI: 0.14–1.18). There was no statistically significant difference in PFS between treatment arms in pts with CR and ctDNA+ at EOT (PFS HR 1.20, 95% CI: 0.49–2.83). Conclusions: Achieving ctDNA− at C5D1 and EOT was prognostic for longer survival. Although no difference was observed in the number of pts with ctDNA− at EOT between arms, pts achieving CR and ctDNA− at EOT had superior PFS in the Pola-R-CHP vs the R-CHOP arm, suggesting deeper molecular responses in pts treated with Pola-R-CHP beyond the detection sensitivity of the assay used in this analysis. Clinical trial information: NCT03274492 . [Table: see text]
A phase I-III platform study evaluating the safety and efficacy of multiple therapies in patients with biomarker-defined locally advanced, unresectable stage III non–small-cell lung cancer (NSCLC).
Authors: Luis G. Paz-Ares, Carl Michael Gay, Caicun Zhou, Terufumi Kato, Luis Corrales, Karl Redhead, Ahmadur Rahman, Denise Bradley, Elizabeth Theogaraj, Katherine E. Hutchinson, Sarah M. Shagan, Benjamin J. Solomon
Journal: Journal of Clinical Oncology (2023)

TPS8605 Background: Durvalumab following chemoradiation (CRT) is a standard of care for unresectable stage III NSCLC, but there remains an unmet need for improved therapeutic options among patients with driver-mutated tumors that are unresponsive to immunotherapy. As targeting of specific driver mutations (e.g. ALK, RET, ROS1) has proven effective in the metastatic setting, it is hypothesized that outcomes could also be improved for patients with driver-mutated stage III NSCLC. Methods: BO42777 (NCT05170204) is a phase I–III platform study evaluating the safety and efficacy of multiple targeted therapies versus durvalumab following CRT in patients with locally advanced, unresectable stage III NSCLC. Biomarker eligibility is determined via local tissue testing or central testing within the BX43361 master screening study (NCT05419375). Biomarker-eligible patients are enrolled into the relevant cohort and randomized 1:1 to receive durvalumab or targeted therapy (alectinib [ ALK+], entrectinib [ ROS1+], or pralsetinib [ RET fusion+]). New cohorts may be added in the future. Key inclusion criteria: locally advanced, unresectable stage III NSCLC, age ≥18 years, ≥2 prior cycles of concurrent or sequential CRT (cCRT or sCRT), and ECOG PS 0–2. Patients are stratified based on staging (IIIA vs IIIB or IIIC), CRT type (cCRT vs sCRT), and PD-L1 status (tumor cell score &lt; 1% vs ≥1% vs unknown) and will receive investigational treatment for three years or durvalumab for one year, until progression or maximum duration of treatment, unacceptable toxicity, consent withdrawal, or death. Primary endpoint: progression-free survival (RECIST v1.1) by blinded independent central review. Key secondary endpoints: distant metastasis-free survival, time to CNS progression, objective response rate, duration of response, overall survival, and safety (adverse events). Time to confirmed deterioration and patient-reported outcomes will be assessed through questionnaires. Tumor response will be assessed by CT/MRI imaging at regular intervals. Enrolment is ongoing (target of 320 patients) across 200 sites in 11 countries. As of 7 February 2023, five patients have been randomized. This trial in progress was previously presented at ELCC, Luis Paz-Ares et al. (#744), and reused with permission. Clinical trial information: NCT05170204 .
Survival outcomes associated with liver-directed therapies in patients with metastatic uveal melanoma.
Authors: Michael M Caplan, Lanyi Nora Chen, Venkatesh Krishnasamy, David Sperling, Joshua Weintraub, David DeStephano, Samuel M Pan, Diana McDonnell, Brian P Marr, Richard D. Carvajal, Shaheer Khan
Journal: Journal of Clinical Oncology (2023)

9590 Background: Metastatic uveal melanoma (mUM) is characterized by a hepatotropic pattern of spread and poor outcomes. Tebentafusp, the only FDA approved therapy, is restricted to patients (pts) with the HLA-A*02:01 genotype. As a result, a variety of liver-directed therapies (LDT) are commonly used for management of hepatic metastases. Methods: Pts with mUM with hepatic metastases who underwent LDT, including radiofrequency ablation, microwave ablation, hepatic metastatectomy, Yttrium-90 radioembolization (SIRT), transarterial chemoembolization (TACE), bland embolization, and immunoembolization (IE), were identified from an institutional database. Data collected included: age, gender, tumor location and size, baseline liver function tests (LFT) and lactate dehydrogenase (LDH), molecular tumor characteristics (where available), type(s) of LDT received, systemic therapies received, and vital status. Time from onset of hepatic metastasis until death (Liver-OS), as well as time from initial diagnosis of primary uveal melanoma until death (Ocular-OS) were calculated. Results: A total of 119 pts were identified. The median age at diagnosis was 53.8 years (range 26-83), 47% were female. At the time of LDT initiation, 33% had bilobar disease and 16% had extrahepatic metastasis. 18% pts had elevated LFTs and 55% had elevated LDH. 72% of pts had M1a disease, 24% had M1b and 4% had M1c disease. 45% of pts received more than one form of LDT. SIRT (31%) was the commonly administered initial LDT, followed closely by IE (26%) and TACE (9%). 86% of pts received systemic therapy including 42% who received immune checkpoint blockade overlapping with LDT. Molecular profiling in 26 pts revealed recurrent mutations in BAP1 (n = 18) and SF3B1 (n = 8). The median ocular-OS across all pts was 71.0 months (95% confidence intervals (CI), 62.8-99.4). The median liver-OS across all pts was 31.8 months (95% CI 25.2-35.3). In pts who received TACE, IE, or SIRT exclusively (n = 44), the median Liver-OS was 15.2 months (95% CI 12.8-NA) for TACE (n = 8), 23.3 months (95% CI 15.8-NA) for SIRT (n = 28), and 28.2 months (95% CI 22.6-NA) for IE (n = 8). Conclusions: Our results provide additional support for the utilization of LDT in pts with mUM, as demonstrated by improved OS compared to historical survival data.
Serum tumor biomarkers as a surrogate for radiographic assessment of non-small cell lung cancer.
Authors: Scott Strum, Mark David Vincent, Meghan Gipson, Eric McArthur, Daniel Adam Breadner
Journal: Journal of Clinical Oncology (2023)

e21076 Background: Conventional tumor markers are positioned to serve as a useful adjunct in lung cancer management. However, most studies in this field have been specific to a particular disease stage or treatment regimen. Thus, the purpose of this research was to assess whether three minimally invasive, low-cost serum tumor markers (CEA, CA19-9, and CA-125) held associations with radiographic and clinical outcomes in non-small cell lung cancer (NSCLC) patients who received systemic therapy in a more comprehensive patient population. Methods: This was a single-center retrospective study of NSCLC patients treated between January 2016 and August 2020. Serum tumor markers were statistically analyzed for differences in patients who responded or progressed (RECIST 1.1 or iRECIST criteria), associations with demographic and clinical characteristics, and all-cause mortality in pre-defined populations. Disease response was assessed radiographically using RECIST 1.1 criteria. Results: From 533 NSCLC patients screened, 165 met inclusion criteria. Of these, 50.9% were male and 49.1% female. 69.7% had stage IV disease at baseline. The proportion of patients with an elevated CEA, CA-125, and CA19-9 at baseline were 58.8%, 50.9%, and 30.3%, respectively. A subset of 92 patients had paired tumor markers and radiographic scans, from which median (IQR) fold-change in tumor markers from nadir to progression was 2.13 (IQR 1.24 - 3.02; p &lt; 0.001) for CEA (n = 47), 1.46 (IQR 1.13 - 2.18; p &lt; 0.001) for CA19-9 (n = 46), and 1.53 (IQR 0.96 - 2.12; p &lt; 0.001) for CA-125 (n = 47). Median (IQR) fold-change in tumor markers from baseline to radiographic response was 0.50 (IQR 0.27, 0.95; p &lt; 0.001) for CEA (n = 39), 1.08 (IQR 0.74, 1.61; p = 0.99) for CA19-9 (n = 35), and 0.47 (IQR 0.18, 1.26; p = 0.008) for CA-125 (n = 35). Lastly, an elevated baseline CEA was not associated with a difference in overall survival (HR 1.05, 95% CI 0.63-1.74, p = 0.84) in patients with stage IV disease within the total population. Conclusions: Serum CEA, CA-125, and CA19-9 levels were significantly different than nadir in patients who progressed. CEA and CA-125 were significantly different than baseline in those who responded. These cost-effective tumor markers may serve as an important adjunct to clinical decision making. Analysis within a controlled clinical trial is warranted.
Long-term outcomes of chronic immune-related adverse events from adjuvant anti-PD-1 therapy for high-risk resected melanoma.
Authors: Rachel S Goodman, Aleigha Lawless, Rachel Woodford, Faisal Fa'ak, Asha Tipirneni, James Randall Patrinely, Hui-Ling Yeoh, Suthee Rapisuwon, Andrew Haydon, Iman Osman, Janice M. Mehnert, Georgina V. Long, Ryan J. Sullivan, Matteo S. Carlino, Alexander M. Menzies, Douglas Buckner Johnson
Journal: Journal of Clinical Oncology (2023)

9591 Background: Adjuvant anti-PD1 improves relapse-free survival in high-risk, resected melanoma, but can lead to irAEs, which become chronic in up to 41% of patients (Patrinely et al, JAMA Onc 2021). Given the expanding use of anti-PD-1 in earlier settings in many tumors, it is imperative to assess their long-term effects. We aimed to determine the incidence, characteristics, and long-term outcomes, including resolution vs persistence, of chronic irAEs from adjuvant anti-PD1. Methods: We retrospectively analyzed patients (pts) treated with adjuvant anti-PD1 for resected stage III-IV melanoma from 2015-2022 from 6 institutions; all pts had at least 18 month follow up post-anti-PD1 discontinuation. Demographics, disease characteristics, treatment and recurrence details, and outcomes were collected. Type, grade, duration, treatment, and resolution of acute (onset during treatment) and chronic irAEs (defined as those extending 6+ months after treatment cessation) were characterized. Results: Among 318 pts, 226 (64%) developed acute irAEs arising during treatment, including 44 (20%) with grade 3-5 irAEs. Chronic irAEs developed in 147 (46%) pts, of which 74 (50%) were grade 2+, 6 (4%) were grade 3-5, and 100 (68%) were symptomatic. With long-term follow-up (median 35 months), 52 (35%) pts experienced resolution of chronic irAEs while 95 (30% of the full cohort) had persistent chronic irAEs at last follow-up. Among these 95 pts with persistent chronic irAEs, 43 (45%) were grade 2+, 42 (44%) were symptomatic, 24 (16%) were on steroids, and 42 (29%) were on other management. The most common persistent chronic irAEs were hypothyroid (n = 38), arthritis (n = 18), dermatitis (n = 9), and adrenal insufficiency (n = 8). Of 37 pts with chronic irAEs who received additional immunotherapy, 12 (32%) had a flare, 10 (27%) had no effect, and 20 (54%) had a distinct irAE. Conclusions: In this large cohort of anti-PD1 treated pts, chronic irAEs were common (46%) and frequently were persistent with long-term follow up (30%, most often hypothyroid and arthritis). Prolonged monitoring and management are needed for these long-term survivors. [Table: see text]